Dr. Varela's immediate career goal is to complete a doctorate in philosophy in Veterinary Parasitology at the University of Georgia, while simultaneously making original contributions to her field of study, specifically, tick-borne disease. This training will be the foundation for her long-term career plans to become an academic biomedical researcher. Having recently completed a D.V.M., supplemented with several research experiences in wildlife parasitology, she is well prepared and eager to further enhance her credentials through an intense, four-year mentored program leading to a doctorate degree in Medical Microbiology and Parasitology. This additional training at the University of Georgia will enable Dr. Varela to further hone her skills in molecular parasitology and experimental animal studies, which will be indispensable in allowing her to develop into an independent medical parasitologist. The overall objective of this proposal is to elucidate the infection dynamics of Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis and the most important emerging tick-borne disease in the southeastern United States, in the natural wild reservoir host, white-tailed deer. Our central hypothesis is that deer and ticks develop a persistent infection with E. chaffeensis that allows for the maintenance of this organism in nature, transmission to vector ticks, and subsequent creation of a human health risk. Our hypothesis of persistent infection will be tested by four specific aims: (1) understand the response to infection with multiple strains of E. chaffeensis in vitro and in vivo; (2) determine the degree of change in the level of organism following initiation of infection in deer and ticks; (3) identify the site of E. chaffeensis replication and maintenance in ticks; and (4) develop a monocyte primary cell culture in vitro model for investigating E. chaffeensis infection in different hosts. We are confident that the quality of the research environment at the University of Georgia, the critical mass of collaborating researchers focusing on the maintenance of ehrlichial organisms in nature, and the depth and breadth of background and training of her sponsor and co-sponsor create a strong research environment that will allow Dr. Varela to develop into an outstanding medical parasitologist and add to the understanding of tick-borne disease and human health.